Current approaches to cancer chemotherapy and other immunological therapies focus on the use of cell-specific antibodies bonded to immunotoxins in order to kill specific populations of human cells. Ideally, immunotoxins should discriminate to a high degree between target and non-target cells. The critical point, then, is the development of immunotoxins that are highly toxic for specific populations of cells. The present invention details a new class of immunotoxins employing a monoclonal antibody, recognizing a specific human cell receptor, bonded to Pseudomonas toxin. Pseudomonas exotoxin (PE) is modified with methyl-4-mercaptobutyrimidate (MMB) so that, by itself, the toxin exhibits very little toxicity; coupling the modified toxin to a monoclonal antibody, however, transforms the toxin into a highly potent immunotoxin.
Other toxins have been modified in order to produce a suitable immunotoxin. The two best known are ricin toxin and diptheria toxin. However, both of these toxins must be cleaved and the A-chain subunits purified prior to bonding with suitable antibodies. With Pseudomonas exotoxin, the cleavage step is unnecessary. In addition, cleavage of ricin or diptheria toxins into A and B chains removes the portion of the molecule containing residues important for transport into the cytosol of the cell. In contrast, when Psuedomonas exotoxin is modified, no part of the molecule is removed; coupling the exotoxin to a suitable monoclonal antibody produces a very potent cell-specific and easily internalized toxin.